We examined the feasibility and acceptability of using an immersive virtual reality environment (VRE) alongside cognitive behaviour therapy (CBT) for young people with autism experiencing specific phobia. Thirty-two participants were randomised to treatment or control. Treatment involved one session introducing CBT techniques and four VRE sessions, delivered by local clinical therapists. Change in target behaviour was independently rated. Two weeks after treatment, four treatment participants (25%) and no control participants were responders; at 6 months after treatment, six (38%) treatment and no control participants were responders. At 6 months post-treatment, symptoms had worsened for one treatment and five control (untreated) participants. Brief VRE exposure with CBT is feasible and acceptable to deliver through child clinical services and is effective for some participants.

The Wnt family of developmental genes has previously been shown to be involved in proliferation, differentiation, and cell to cell signaling during embryogenesis. In addition, several Wnt genes have been shown to be expressed during carcinogenesis. We have investigated these genes during the wound-healing process. Wnt-4 gene expression is found in mouse wounds from 2 hours to 30 hours postwounding. The expression of Wnt-4 is also stimulated by direct trauma to murine fibroblasts in culture, and the expression is greatly enhanced by the addition of a short plasmin digest of fibrin. Therefore the regulation of Wnt-4, appears to be complex, with expression being stimulated both by direct trauma and by the influence of clotting and fibrinolysis products. We propose that the expression of Wnt-4 in the early wound, in response to the provisional fibrin matrix, regulates cell movement and proliferation in the creation of new tissue by mechanisms related to those of embryogenesis.

Summary Background The updated American Joint Committee on Cancer (AJCC) staging criteria for melanoma remain unable to identify high‐risk stage I tumour subsets. Objectives To determine the utility of epidermal autophagy and beclin 1 regulator 1 (AMBRA1)/loricrin (AMLo) expression as a prognostic biomarker for AJCC stage I cutaneous melanoma. Methods Peritumoral AMBRA1 expression was evaluated in a retrospective discovery cohort of 76 AJCC stage I melanomas. AMLo expression was correlated with clinical outcomes up to 12 years in two independent powered, retrospective validation and qualification cohorts comprising 379 AJCC stage I melanomas. Results Decreased AMBRA1 expression in the epidermis overlying primary melanomas in a discovery cohort of 76 AJCC stage I tumours was associated with a 7‐year disease‐free survival (DFS) rate of 81·5% vs. 100% survival with maintained AMBRA1 (P < 0·081). Following an immunohistochemistry protocol for semi‐quantitative analysis of AMLo, analysis was undertaken in validation (n = 218) and qualification cohorts (n = 161) of AJCC stage I melanomas. Combined cohort analysis revealed a DFS rate of 98·3% in the AMLo low‐risk group (n = 239) vs. 85·4% in the AMLo high‐risk cohort (n = 140; P < 0·001). Subcohort multivariate analysis revealed that an AMLo hazard ratio (HR) of 4·04 [95% confidence interval (CI) 1·69–9·66; P = 0·002] is a stronger predictor of DFS than Breslow depth (HR 2·97, 95% CI 0·93–9·56; P = 0·068) in stage IB patients. Conclusions Loss of AMLo expression in the epidermis overlying primary AJCC stage I melanomas identifies high‐risk tumour subsets independently of Breslow depth. What's already known about this topic? There is an unmet clinical need for biomarkers of early‐stage melanoma. Autophagy and beclin 1 regulator 1 (AMBRA1) is a proautophagy regulatory protein with known roles in cell proliferation and differentiation, and is a known tumour suppressor. Loricrin is a marker of epidermal terminal differentiation. What does this study add? AMBRA1 has a functional role in keratinocyte/epidermal proliferation and differentiation. The combined decrease/loss of peritumoral AMBRA1 and loricrin is associated with a significantly increased risk of metastatic spread in American Joint Committee on Cancer (AJCC) stage I tumours vs. melanomas, in which peritumoral AMBRA1 and loricrin are maintained, independently of Breslow depth. What is the translational message? The integration of peritumoral epidermal AMBRA1/loricrin biomarker expression into melanoma care guidelines will facilitate more accurate, personalized risk stratification for patients with AJCC stage I melanomas, thereby facilitating stratification for appropriate follow‐up and informing postdiagnostic investigations, including sentinel lymph node biopsy, ultimately resulting in improved disease outcomes and rationalization of healthcare costs.

Fears and phobias are common in people on the autism spectrum and can impact on their ability to undertake usual daily activities. Graded exposure to the anxiety-provoking stimulus is a recognized method of treatment for fears/phobias in the nonautistic population but may pose specific difficulties for autistic people. For example, real-life exposure can be too anxiety-provoking to allow treatment to take place, and imaginal exposure can be problematic. To address this, we developed an intervention that combines cognitive behavioral therapy (CBT) with immersive virtual reality (VR) exposure to reduce anxiety. Following successful trials of this intervention with young people on the autism spectrum, we report a pilot study using the same intervention with autistic adults. Eight adults (aged 18–57 years) received one psychoeducation session and then four 20-minute sessions of graded exposure with a therapist in an immersive VR room (known as the Blue Room). Each participant completed all sessions showing that the intervention is feasible and acceptable. Outcomes were monitored at 6 weeks and 6 months postintervention. Five of the eight participants were classified as intervention responders and at 6 months after the end of intervention were experiencing real-life functional improvements. These preliminary findings show that VR-graded exposure alongside CBT may be an effective treatment for autistic people with phobias. Lay Summary Why was this study done? Anxiety is common in autistic adults. For some people, fears and phobias regarding everyday objects and situations occur frequently affecting everyday life. The main method to treat fears and phobias for people without autism is gradual exposure to the situation that causes anxiety. However, this method may be challenging for people on the autism spectrum. We wanted to test a new method of treatment that uses cognitive behavioral therapy (CBT) delivered with gradual exposure in a fully immersive virtual reality (VR) environment. What was the purpose of this study? We have already delivered this treatment successfully with autistic children. We wanted to test if this treatment would work for autistic adults. Changing traditional psychological treatments, such as CBT, to make it more suitable for autistic people is recommended by the National Institute for Health and Care Excellence. What did the researchers do? We recruited eight autistic adults (aged 18–57 years) with a fear/phobia and their supporter (parent/friend/support worker). Each adult had one session with a therapist to learn anxiety management techniques. They then had four 20-minute sessions of graded exposure with a therapist in an immersive VR room (known as the Blue Room). Each participant had a computer-generated scene designed for their specific anxiety-provoking situation. After four sessions, the participant tried real-life exposure with their supporter. We measured progress at 6 w...

Oropharyngeal squamous cell carcinoma (OPSCC) is an increasing world health problem with a more favorable prognosis for patients with human papillomavirus (HPV)-positive tumors compared to those with HPV-negative OPSCC. How HPV confers a less aggressive phenotype, however, remains undefined. We demonstrated that HPVpositive OPSCC cells display reduced macroautophagy/autophagy activity, mediated by the ability of HPV-E7 to interact with AMBRA1, to compete with its binding to BECN1 and to trigger its calpain-dependent degradation. Moreover, we have shown that AMBRA1 downregulation and pharmacological inhibition of autophagy sensitized HPV-negative OPSCC cells to the cytotoxic effects of cisplatin. Importantly, semi-quantitative immunohistochemical analysis in primary OPSCCs confirmed that AMBRA1 expression is reduced in HPV-positive compared to HPVnegative tumors. Collectively, these data identify AMBRA1 as a key target of HPV to impair autophagy and propose the targeting of autophagy as a viable therapeutic strategy to improve treatment response of HPV-negative OPSCC. Abbreviations: AMBRA1: autophagy and beclin 1 regulator 1; CDDP: cisplatin (CDDP); FFPE: formalin-fixed paraffin-embedded (FFPE); HNC: head and neck cancers (HNC); HPV: human papillomavirus (HPV); hrHPV: high risk human papillomavirus (hrHPV); OCSCC: oral cavity squamous carcinomas (OCSSC); OPSCC: oropharyngeal squamous cell carcinoma (OPSCC); OS: overall survival (OS); qPCR: quantitative polymerase chain reaction; RB1: RB transcriptional corepressor 1; ROC: receiver operating characteristic curve (ROC).